BACKGROUND: Steroid receptor-associated and regulated protein (SRARP) suppresses tumor progression and modulates steroid receptor signaling by interacting with estrogen receptors and androgen receptors in breast cancer. In endometrial cancer (EC), progesterone receptor (PR) signaling is crucial for responsiveness to progestin therapy. The aim of this study was to investigate the role of SRARP in tumor progression and PR signaling in EC. METHODS: Ribonucleic acid sequencing data from the Cancer Genome Atlas, Clinical Proteomic Tumor Analysis Consortium, and Gene Expression Omnibus were used to analyze the clinical significance of SRARP and its correlation with PR expression in EC. The correlation between SRARP and PR expression was validated in EC samples obtained from Peking University People's Hospital. SRARP function was investigated by lentivirus-mediated overexpression in Ishikawa and HEC-50B cells. Cell Counting Kit-8 assays, cell cycle analyses, wound healing assays, and Transwell assays were used to evaluate cell proliferation, migration, and invasion. Western blotting and quantitative real-time polymerase chain reaction were used to evaluate gene expression. The effects of SRARP on the regulation of PR signaling were determined by co-immunoprecipitation, PR response element (PRE) luciferase reporter assay, and PR downstream gene detection. RESULTS: Higher SRARP expression was significantly associated with better overall survival and disease-free survival and less aggressive EC types. SRARP overexpression suppressed growth, migration, and invasion in EC cells, increased E-cadherin expression, and decreased N-cadherin and Wnt family member 7A ( WNT7A ) expression. SRARP expression was positively correlated with PR expression in EC tissues. In SRARP -overexpressing cells, PR isoform B (PRB) was upregulated and SRARP bound to PRB. Significant increases in PRE-based luciferase activity and expression levels of PR target genes were observed in response to medroxyprogesterone acetate. CONCLUSIONS This study illustrates that SRARP exerts a tumor-suppressive effect by inhibiting the epithelial-mesenchymal transition via Wnt signaling in EC. In addition, SRARP positively modulates PR expression and interacts with PR to regulate PR downstream target genes.
Female ; Humans ; Receptors, Progesterone/metabolism* ; Proteomics ; Cell Line, Tumor ; Endometrial Neoplasms/metabolism* ; Cell Proliferation/genetics* ; Luciferases/pharmacology* ; Gene Expression Regulation, Neoplastic/genetics*

Animals ; Autophagy/genetics* ; Cholesterol/metabolism* ; Gene Expression Regulation ; Integrases/metabolism* ; Leydig Cells/metabolism* ; Male ; Mice, Knockout ; Multienzyme Complexes/metabolism* ; Phosphoproteins/metabolism* ; Primary Cell Culture ; Progesterone Reductase/metabolism* ; RNA Splicing Factors/metabolism* ; Scavenger Receptors, Class B/metabolism* ; Sequestosome-1 Protein/metabolism* ; Signal Transduction ; Sirtuin 1/genetics* ; Sodium-Hydrogen Exchangers/metabolism* ; Steroid 17-alpha-Hydroxylase/metabolism* ; Steroid Isomerases/metabolism* ; Testosterone/genetics*

OBJECTIVE: To evaluate the relationship between response categories assessed by magnetic resonance imaging (MRI) or pathology and survival outcomes, and to determine whether there are prognostic differences among molecular subtypes. MATERIALS AND METHODS: We evaluated 174 patients with biopsy-confirmed invasive breast cancer who had undergone MRI before and after neoadjuvant chemotherapy, but before surgery. Pathology findings were classified as a pathologic complete response (pCR) or a non-pCR, and MRI findings were designated as a radiologic CR (rCR) or a non-rCR. We evaluated overall and subtype-specific associations between clinicopathological factors including the assessment categories and recurrence, using the Cox proportional hazards model. RESULTS: There were 41 recurrences (9 locoregional and 32 distant recurrences). There were statistically significant differences in recurrence outcomes between patients who achieved a radiologic or a pCR and patients who did not achieve a radiologic or a pCR (recurrence hazard ratio, 11.02; p = 0.018 and recurrence hazard ratio, 3.93; p = 0.022, respectively). Kaplan-Meier curves for recurrence-free survival showed that triple-negative breast cancer was the only subtype that showed significantly better outcomes in patients who achieved a CR compared to patients who did not achieve a CR by both radiologic and pathologic assessments (p = 0.004 and 0.001, respectively). A multivariate analysis found that patients who achieved a rCR and a pCR did not display significantly different recurrence outcomes (recurrence hazard ratio, 2.02; p = 0.505 and recurrence hazard ratio, 1.12; p = 0.869, respectively). CONCLUSION: Outcomes of patients who achieved a rCR were similar to those of patients who achieved a pCR. To evaluate survival difference according to molecular subtypes, a larger study is needed.
Adult ; Aged ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy/mortality/*pathology ; Female ; Humans ; Kaplan-Meier Estimate ; *Magnetic Resonance Imaging ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Remission Induction

OBJECTIVETo investigate the effect of estrogen (E2), progesterone(P4), and paclitaxel (taxol) on the growth of primary human ovarian cancer cells in vitro and the expression of Drosha.

METHODSHuman ovarian cancer cells were treated with estrogen, progesterone or in combination with paclitaxel in vitro. The inhibition rate of ovarian cancer cells was assessed by methyl thiazolyl tetrazolium (MTT) assay. Apoptosis rate and cell cycle were determined by FACS analysis. The relative abundence of Drosha expression was detected by real-time quantitative PCR (qRT-PCR) and Western blotting.

RESULTSThe inhibition rate of the estrogen group, progesterone group, paclitaxel group, E2(+)Taxol group, P4(+)Taxol group was (31.53 ± 8.21)%, (25.22 ± 15.50)%, (46.71 ± 4.25)%, (69.46 ± 3.71)%, and (47.35 ± 39.02)%, respectively, significantly higher than that of the control group (0%, P<0.05 for all). Relative to the ER (-) in ovarian cancer cells,Drosha mRNA expression level of estrogen group, progesterone group, paclitaxel group, E2(+) Taxol group,and P4(+)Taxol group was 1.62 ± 0.10,1.60 ± 0.10,1.75 ± 0.16,1.95 ± 0.20, and 1.53 ± 0.06, respectively, significantly higher than that of the control group (1.00, P<0.05 for all). Relative to the ER (+)in ovarian cancer cells,the Drosha mRNA expression level of estrogen group, progesterone group, paclitaxel group, E2(+)taxol group, and P4(+)Taxol group was 1.03 ± 0.14, 1.60 ± 0.09, 1.75 ± 0.16, 1.60 ± 0.10, 1.53 ± 0.06, respectively except estrogen group, significantly higher than that of the control group (1.00, P<0.05). Relative to the ER (-) in ovarian cancer cells, the Drosha protein expression levels of the control group, estrogen group, progesterone group, paclitaxel group, E2(+) taxol group, and P4(+) Taxol group were 0.25 ± 0.05, 0.87 ± 0.30, 0.85 ± 0.38, 1.30 ± 0.21, 1.75 ± 0.83, 1.62 ± 0.82, respectively, with a significant difference between the experimental groups and the control group (P<0.05). Relative to the ER(+)ovarian cancer cells, the Drosha protein expression levels in the estrogen group, progesterone group, paclitaxel group, E2(+) taxol group, and P4(+) taxol group, were 0.28 ± 0.16, 0.85 ± 0.38, 1.30 ± 0.21, 0.94 ± 0.18, and 1.62 ± 0.82, respectively except estrogen group, significantly higher than that of the control group (0.25 ± 0.05, P<0.05 for all).

CONCLUSIONSEstrogen and progesterone in combination with paclitaxel can inhibit the growth of human ovarian cancer cells in vitro, and affect the cell apoptosis rate. Estrogen and taxol can alter the cell cycle. Estrogen and progesterone combined with paclitaxel show tumor suppressing or sensitizing effect through upregulated Drosha expression, and are associated with the estrogen receptor expression.

Antineoplastic Agents, Phytogenic ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Apoptosis ; Cell Cycle ; Cell Growth Processes ; drug effects ; Cell Line, Tumor ; Coloring Agents ; Drug Therapy, Combination ; Estrogens ; pharmacology ; Female ; Humans ; In Vitro Techniques ; Ovarian Neoplasms ; chemistry ; drug therapy ; metabolism ; pathology ; Paclitaxel ; pharmacology ; Progesterone ; pharmacology ; RNA, Messenger ; metabolism ; Receptors, Estrogen ; metabolism ; Ribonuclease III ; genetics ; metabolism ; Tetrazolium Salts ; Thiazoles ; Up-Regulation

OBJECTIVETo investigate the effect of acupuncture on progesterone (P4) and prolactin (PRL) in rats of embryo implantation dysfunction (EID).

METHODSOn the first day of pregnancy, 72 female Wistar rats were randomly allocated into the normal group, the EID model group, the acupuncture group and the P4 group (18 in each group). The normal group was injected sesame oil, while the other three groups were given mifepristone to establish the EID model. The acupuncture group and the P4 group were given treatment of acupuncture and P4 injection, respectively. The serum of P4 and PRL were detected by radioimmunoassay, and the mRNA and protein expressions of P4 receptor (PR) and PRL receptor (PRLR) were detected using real-time polymerase chain reaction and immunohistochemical method, respectively.

RESULTSCompared with the normal group, the serum levels of P4 and PRL as well as the mRNA and protein expression levels of PR and PRLR in the EID model group were significantly lowered (P<0.01 or P<0.05). The above indices in the acupuncture group and the P4 group were significantly elevated compared with the EID model group (P<0.01 or P<0.05).

CONCLUSIONAcupuncture can promote embryo implantation effectively, which might be related to the effects of acupuncture on upregulating the P4 and PRL levels in serum and the PR and PRLR expression levels in rats.

Acupuncture Therapy ; Animals ; Embryo Implantation ; Endometrium ; metabolism ; Female ; Gene Expression Regulation ; Immunohistochemistry ; Male ; Pituitary Gland ; metabolism ; Pregnancy ; Progesterone ; blood ; Prolactin ; blood ; RNA, Messenger ; genetics ; metabolism ; Rats, Wistar ; Receptors, Progesterone ; genetics ; metabolism ; Receptors, Prolactin ; genetics ; metabolism

Breast Neoplasms ; metabolism ; Female ; Humans ; Multidrug Resistance-Associated Proteins ; genetics ; metabolism ; Receptor, Epidermal Growth Factor ; metabolism ; Receptors, Progesterone ; metabolism

Age of Onset ; Cystadenocarcinoma, Serous ; genetics ; metabolism ; pathology ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Immunohistochemistry ; Neoplasm Staging ; Ovarian Neoplasms ; genetics ; metabolism ; pathology ; Receptors, Progesterone ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo explore the clinicopathologic characteristics and biological markers of breast carcinomas in young women.

METHODSImmunohistochemical SP method was used to study breast cancer susceptibility gene (BRCA1) and WWOX in breast carcinomas of patient ≤ 35 years of age (107 cases) and ≥ 60 years of age (112 cases). The findings were correlated with clinicopathological features. In addition, PCR amplification and direct sequencing were performed to detect the BRCA1 gene mutation of exons 2 and 20 using fresh frozen tissue samples in other 10 patients who were ≤ 35 years of age.

RESULTSThe positive rate of BRCA1 protein expression was higher in the young age group [65.4% (70/107)] than that of the old age group [35.7% (40/112)]. ER, PR, HER2, and WWOX protein expression and proliferation marker Ki-67 were no statistically different in the two groups (all P > 0.05). BRCA1 expression was significantly correlated with pTNM and axillary lymph node metastasis (both P < 0.05), but not with ER, PR, HER2 and WWOX protein expression (all P > 0.05). Ki-67 and histological grading showed no statistical correlation (P > 0.05). WWOX protein expression showed no correlation with clinicopathologic characteristics (all P > 0.05). Mutation of exons 2 and 20 of the BRCA1 gene was not detected in any of 10 cases studied.

CONCLUSIONBRCA1 cytoplasmic expression statistically correlates with the development and prognosis of breast cancer of young patients.

Adult ; Age Factors ; Aged ; Aged, 80 and over ; BRCA1 Protein ; genetics ; metabolism ; Breast Neoplasms ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; surgery ; Exons ; Female ; Genes, BRCA1 ; Humans ; Ki-67 Antigen ; metabolism ; Lymphatic Metastasis ; Middle Aged ; Mutation ; Neoplasm Staging ; Oxidoreductases ; metabolism ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Tumor Suppressor Proteins ; metabolism ; WW Domain-Containing Oxidoreductase ; Young Adult

OBJECTIVE: To observe the expression of progesterone receptor (PR), interleukin-1β (IL-1β), and cyclooxygenase-2 (COX-2) induced by lipopolysaccharide (LPS) or Toll-like receptor 4 antagonist (TLR4 mAb) in decidual cells in vitro, and then to explore the effect of LPS and its antagonist on PR of decidual cells and the relation between PR and inflammatory cytokines. METHODS: We isolated and cultured human decidua of early abortion in the sterile state. When the cells passaged to the 4th generation, the cells were randomly divided into 6 pore plates: A control group was added the culture medium alone; experimental group I was added 100 ng/mL of LPS; experimental group II was add 1 μg/mL of TLR4 mAb; experimental group III was added 3 μg/ mL of TLR4 mAb; experimental group IV was added 1 μg/mL of TLR4 mAb pretreatment for 24 h, and then 100 ng/mL LPS; and experimental group V was added 3 μg/mL of TLR4 mAb pretreatment for 24 h, and then 100 ng/mL LPS for 24 h culture. Subsequently, HE staining and immunofluorescence were used to observe the morphology and identify the purity of decidual cells in the 6 groups. The levels of mRNA expression of PR, IL-1β, and COX-2 were detected by reverse transcription PCR (RT-PCR). RESULTS: LPS reduced the mRNA expression of PR (P<0.05), increased the mRNA expression of IL-1β and COX-2 (P<0.05). TLR4 mAb increased the mRNA expression of PR (P<0.05) and reduced the mRNA expression of IL-1β (P<0.05) after LPS-stimulated decidual cells. High concentrations of TLR4 mAb reduced the mRNA expression of COX-2 (P<0.05) after LPS stimulated decidual cells. CONCLUSION The mRNA expression of PR is reduced, and the mRNA expressions of IL-1β and COX-2 are increased after LPS-stimulated decidual cells in vitro. TLR4 mAb antagonize the role of LPS on PR, IL-1β, and COX-2.
Adult ; Cells, Cultured ; Cyclooxygenase 2 ; genetics ; metabolism ; Decidua ; cytology ; metabolism ; Female ; Humans ; Interleukin-1beta ; genetics ; metabolism ; Lipopolysaccharides ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Receptors, Progesterone ; genetics ; metabolism ; Toll-Like Receptor 4 ; antagonists & inhibitors ; Young Adult

OBJECTIVETo study the effect of BRCA1 in regulating the proliferation and migration of breast cancer cells stimulated by progesterone.

METHODSBreast cancer MCF-7 and T-47D cell were transfected with a vector containing the coding sequence of BRCA1 (pFlag-CMV2-BRCA1 wt) to induce BRCA1 overexpression or with the empty vector (control). The cells were then stimulated with progesterone, and the cell proliferation and migration were observed using MTT assay and wound healing assay, respectively. The proliferation and migration of MCF-7 cells were also observed following transfection with a small interfering RNA (siRNA) for BRCA1 knockdown or with a scrambled siRNA prior to progesterone stimulation.

RESULTSTransfection with the empty vector and with pFlag-CMV2-BRCA1 wt prior to progesterone stimulation caused significantly different proliferation rates in MCF-7 cells [(114.4∓6.0)% vs (82.1∓3.2)%, P<0.05] and in T-47D cells [(111.3∓4.3)% vs (84.2∓3.5)%, P<0.05], resulting also in significantly different cell migration rates (55.9% vs 15.8% in MCF-7 cells and 44.83% vs 10.43% in T-47D cells). Compared to the scrambled siRNA, BRCA1 siRNA transfection prior to progesterone stimulation significantly increased the proliferation rates [(114.4∓3.05)% vs (125.3∓4.0)%, P<0.05] and migration rate (39.2% vs 69.08%) of MCF-7 cells. The progesterone antagonist RU468 could antagonize the effects of BRCA1 knockdown in enhancing progesterone-stimulated MCF-7 cell proliferation and migration.

CONCLUSIONA decreased BRCA1 expression can enhance progesterone-stimulated tumor cell proliferation and migration in sporadic breast cancer.

BRCA1 Protein ; metabolism ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Female ; Genetic Vectors ; Humans ; Progesterone ; pharmacology ; RNA, Messenger ; genetics ; Receptors, Progesterone ; antagonists & inhibitors ; Transfection